Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis

“I am often asked ‘How do you feel with amyotrophic lateral sclerosis?’ My answer is ‘Not actually good’.”

Stephen Hawking,
world-renowned astrophysicist

Amyotrophic lateral sclerosis (ALS) is a rare (orphane) incurable slowly progressive degenerative disease of the central nervous system with the lesion of both upper (motor cortex) and lower (ventral horns of the spinal cord and cranial nerve nuclei) motor neurons.

It results in progressive weakness of the bulbar (mouth, larynx, throat), thoracic, abdominal muscles and limb muscles. The rest of the brain functions are relatively preserved. In the later stages of the disease, respiratory muscles are affected, patients experience respiratory failure, ultimately, their lives can only be supported by artificial ventilation (ventilator) and artificial nutrition.

The incidence is 2-5 per 100 thousand people per year, with a tendency to its growth in all age groups. ALS is usually identified in patients over 40 years of age. Death occurs on average 2-4 years after the onset of symptoms through respiratory failure, but 5-10% of patients can survive for ten years or more.

The causes of the disease are not fully understood. Currently, the multifactorial theory of ALS – a combination of external factors (influence of various exotoxins and viruses) with genetic predisposition – is most reasonable. The effect of the gene that encodes formation of superoxide dismutase 1 (SOD1) is most studied. Superoxide dismutase belongs to the group of antioxidant enzymes. It is an enzyme element of the antioxidant system of the body, and together with catalase and glutathione peroxidase, it protects the human body from constantly forming highly toxic free radicals.

The exact mechanisms by which SOD1 contributes to the progression of ALS are currently unknown. It was found that SOD1 plays a key role in the inactivation of superoxide free radicals; therefore, defective enzymatic activity leads to increased levels of oxidative stress, which causes damage to nerve cells. The presence of oxidative stress biomarkers has been confirmed in the cerebrospinal fluid of patients with ALS.